The purpose of this project is to identify, isolate and characterize murine lentiviruses. Although several excellent models for HIV exist, research with the alternate lentivirus models, such as SIV and FIV, is restricted by the limited access constraints. The wild, or feral, mouse has repeatedly provided model systems for the study of naturally occurring retroviruses and associated diseases. Our own research has provided feral mouse models for murine leukemia, mammary tumorigenesis and retrovirus-induced lower neuron paralytic disease. Thus, a comprehensive search for a murine lentivirus in feral mice seems warranted. We have begun such a search using polymerase chain reaction primed by universal lentivirus polymerase oligonucleotides and probed by caprine arthritis encephalitis virus polymerase sequences to analyze DNA from wild mice (Mus musculus domesticus) trapped at a squab farm near Lake Casista (LC) in southern California These mice were used in the DNA from 7 of 54 animals. Two such nucleotide segments have been cloned and sequenced. One resembles a hepadnavirus and the other a retrovirus ( and possibly a lentivirus). We now propose to extend this search by 1) further characterization of DNAs flanking the current clones, 2) searching for other PCR positive animals, 3) doing a serologic survey of wild mouse populations for antibodies cross reactive with existing lentiviruses and 4) culturing and characterizing candidate infectious agents from selected mice. Should we identify a candidate murine lentivirus, it will be thoroughly biologically and molecularly characterized.